MR imaging and proton spectroscopy of neuronal injury in late-onset G _M2 gangliosidosis

BACKGROUND AND PURPOSE: Despite the ubiquity of G_M2 gangliosides accumulation in patients with late-onset G_M2 gangliosidosis (G _M2G), the only clinical MR imaging-apparent brain abnormality is profound cerebellar atrophy. The goal of this study was to detect the presence and assess the extent of neuroaxonal injury in the normal-appearing gray and white matter (NAGM and NAWM) of these patients. METHODS: During a single imaging session, 9 patients with late-onset G_M2G and 8 age-matched normal volunteers underwent the following protocol: (1) T1- and T2-weighted and fluid-attenuated inversion recovery MR images, as well as (2) multivoxel proton MR spectroscopy (¹H-MR spectroscopy) to quantify the distribution of the N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), were obtained. RESULTS: The patients' NAA levels in the thalamus (6.5 ± 1.9 mmol/L) and NAWM (5.8 ± 2.1 mmol/L) were ∼40% lower than the controls' (P = .003 and P = .005), whereas the Cr and Cho reductions (∼30% and ∼26%) did not reach significance (P values of .06-.1). All cerebellar metabolites, especially NAA and Cr, were much (30%-90%) lower in the patients, which reflects the atrophy. CONCLUSION: In late-onset G_M2G, NAA decreases are detectable in NAGM and NAWM even absent morphologic (MR imaging) abnormalities. Because the accumulation of G_M2 gangliosides can be reduced pharmacologically. ¹H-MR spectroscopy might be a sensitive and specific for detecting and quantifying neuroaxonal injury and monitoring response to emerging treatments.